Worldwide, head and neck cancer is a major health problem. The incidence rate of head and neck squamous carcinoma (SCCHN) is higher among Puerto Rican Hispanics than among Hispanics living in the US. Advances in locoregional control of SCCHN have not increased patients' survival due to recurrence, metastases or second primary tumors (SPTs). Development of SCCHN involves the interplay between genetic events and environmental factors. Tobacco and alcohol are the main risk factors. Recently, human papillomavirus type 16 (HPV16) has been implicated in the etiology of 20-30% SCCHNs. Gene-environment interactions play a significant role in determining susceptibility to SCCHN. Variants in DNA repair genes, and metabolic genes associated with tobacco and alcohol metabolism could be associated with the individual susceptibility to develop cancer. The underlying hypothesis is that individuals with susceptible genotypes and behavioral risk factors are at greater risk of disease progression and SPTs. In HPV16-positive SCCHN patients, HPV16 DNA serum levels may be a potential biomarker for metastasis. To test our hypothesis we plan a follow-up study of 250 Puerto Rican patients with the following specific aims: 1) Gather baseline and follow-up epidemiological and clinical data on Puerto Rican SCCHN patients (200 new patients and 50 already accrued); 2) Determine HPV16 positive tumors and specific variants; 3) Measure the serum levels of HPV16 DNA in HPV16-positive patients; 4) Correlate HPV16 infection and p53 mutations with clinical data of SCCHN Puerto Rican patients; 5) Analyze selected constitutional polymorphic genes associated with tobacco and alcohol metabolism, and DNA repair (e.g. GSTs, ADH3, XRCC1, XPD, and p53); and 6) analyze epidemiologist and biomarker data as predictors of recurrence and development of SPTs. These patients will be followed for the development of recurrences, metastasis and SPTs. We will be able to obtain preliminary and to compare lifestyle characteristics and molecular markers in this Hispanic population. The long-term goal of this line of research is to identify markers for predicting the risk of recurrence or SPTs that could be used to develop specific intervention strategies to target high-risk patients. This project will provide the opportunity to develop the infrastructure for an epidemiological study at the UPRCC. These preliminary data will be the basis for an R01 proposal.